Genital HSV infections continue to be epidemic throughout the world. Recent studies have suggested that >70% of the transmission of infection to sexual partners and neonates is associated with unrecognized or asymptomatic shedding of virus from mucosal surfaces. With support from this proposal, we initiated a series of studies to evaluate the national history of subclinical HSV-2. Our recent studies suggest that HSV reactivates in the cervical, vulvar, penile, rectal and urethral areas. Using PCR techniques, subclinical reactivation can be detected in 8-15% of days sampled, suggest that from an epidemiologic point of view HSV may be more of a persistent than intermittent infection. Recent prospective studies of pregnant women indicate that subclinical acquisition of HSV during pregnancy occurs frequently, appears to be associated with stillbirth and accounts for over 75% of neonatal HSV transmissions. In a preliminary study of HSV infection in men and women, we detected HSV-2 by culture on 10% of the days and HIV infected pregnant women shed HSV at term 5 times more frequently than HIV seronegative HSV women thereby exposing their infants to potential acquisition of herpes neonatal. In addition, we have been able to isolate HIV from mucosal surfaces during episodes of HSV-2 reactivation. Proposed studies are 1) to evaluate the importance of subclinical herpes in the transmission of infection to sexual partners and infants, 2) to develop strategies to interrupt acquisition of genital herpes in pregnancy, 3) to define the complication of HSV in HIV infected men and women and to evaluate the role HSV reactivation plays in up regulating HIV replication on mucosal surfaces, 4) to correlate host mucosal antibody responses to subclinical reactivation, and 5) to utilize the above information in the design and evaluation of candidate HSV vaccine and intervention programs.